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Here, we show that both associations are functionally linked. Transcriptional profiling revealed that high <jats:italic>CD163<\/jats:italic> and <jats:italic>CD206\/MRC1<\/jats:italic> expression in TAMs is strongly associated with an inhibition of cytokine\u2010triggered signaling, mirrored by an impaired transcriptional response to interferons and IL\u20106 in monocyte\u2010derived macrophages by AA. This inhibition of pro\u2010inflammatory signaling is caused by dysfunctions of the cognate receptors, indicated by the inhibition of JAK1, JAK2, STAT1, and STAT3 phosphorylation, and by the displacement of the interferon receptor IFNAR1, STAT1 and other immune\u2010regulatory proteins from lipid rafts. AA exposure led to a dramatic accumulation of free AA in lipid rafts, which appears to be mechanistically crucial, as the inhibition of its incorporation into phospholipids did not affect the AA\u2010mediated interference with STAT1 phosphorylation. Inhibition of interferon\u2010triggered STAT1 phosphorylation by AA was reversed by water\u2010soluble cholesterol, known to prevent the perturbation of lipid raft structure by AA. 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